Abstracts

The number of centers performing stereotactic radiosurgery continues to increase, as does interest in radiosurgery as an alternative to invasive surgery for the treatment of refractory epilepsy. The basis for the anti-epileptic effects of radiation as currently practiced is likely related to the necrotizing effects of ionizing radiation. The present studies were undertaken to determine whether sub-necrotizing doses of inonizing radiation can produce long term effects on CNS tissue excitability. Animal radiation procedures were performed as previously detailed by Kennedy et al (Invest Radiol 30:214-20, 1995). Hemibrain radiation dose (0, 10, 20, or 30 Gy) was delivered to Sprague-Dawley rats in a single fraction with a modulated proton beam. Eight months after treatment, animals were either subjected to amygdala kindling (stimulating electrode located in the irradiated hemisphere) OR administered a chemical convulsant (kainic acid, 8 mg/kg i.v.) and monitored for one hour to assess hemispheric EEG spike activity and to grade seizure activity. Prior radiation exposure was found to exert a dose dependent effect on amygdala kindling (See Table 1, ADT = afterdischarge threshold, ADD = afterdischarge durgation). Similary, radiation treatment reduced the severity/duration of the motor convulsions observed during the first hour after kainate administration (p[lt]0.05, Kruskall-Wallis test) as well as the epileptic spike activity in the irradiated but not the contralateral hemisphere (10 Gy = 66% decrease, 20 Gy = 55% decrease vs sham irradiated animals, p [lt] 0.05, 1-way ANOVA , Fisher PLSD tests). Post-mortem histology showed no indication of radiation necrosis in any of the treated animals. [table1] It has been previously shown that radiation doses up to and including 30 Gy produce NO detectable behavioral, histological, or radiolgocial (MRI) indication of radiation necrosis for up to 300 days following irradiation under identical treatment conditions used in the present study, and we conclude that the effects of radiation treatment on amygdala kindling and kainic acid seiaures observed in these studies occur below the necrotizing dose threshold for proton hemibrain irradiation. (Supported by H.L. Guenther Foundation)